Mitogen-activated protein kinase pathway (MAPK pathway) (MAPK)

The Mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that transmits extracellular signals to the nucleus to regulate cell proliferation, differentiation, and survival [1]. In many human cancers, this pathway is pathologically activated by mutations in upstream regulators like RAS or RAF, leading to uncontrolled tumor growth [2]. The term "MAPK pathway-activated tumor cells" describes a cellular state where malignancy is driven by the constitutive activity of this signaling module rather than a single molecular target [3]. Targeting this pathway has become a cornerstone of precision oncology, with drugs designed to inhibit specific nodes such as BRAF, MEK, or ERK [4]. These inhibitors work by blocking the phosphorylation of downstream targets, thereby inducing cell cycle arrest and apoptosis in "addicted" tumor cells [1]. However, clinical efficacy is often limited by the emergence of drug resistance, which can occur through pathway reactivation or the activation of alternative survival pathways like PI3K/AKT [2]. Monitoring biomarkers such as BRAF V600E or KRAS mutations is essential for identifying patients whose tumor cells are likely to respond to these targeted agents [3]. Safety concerns associated with these therapies include paradoxical activation of the pathway in healthy tissues and various systemic toxicities [4].

Other names

Ras-Raf-MEK-ERK pathwayERK signaling cascadeMitogen-activated protein kinase signaling pathwayMAPK/ERK pathway

Inhibition of specific kinase components (such as BRAF, MEK, or ERK) within the signaling cascade to prevent downstream phosphorylation and gene transcription, leading to growth arrest and apoptosis in cells dependent on this pathway.